We are now seeking a new PPG to support our present virological studies among 7 members of our faculty. The core component is for partial support of the shared tissue culture, electron microscopy (EM), X-ray crystallographic, computing and NMR facilities. The X-ray and computing facilities are also shared with five other members of the Purdue Structural Biology group who will also contribute proportionally to maintaining these services. The NMR facilities, to which we have full access, are kept jointly by the Departments of Chemistry and Medicinal Chemistry and Molecular Pharmacology. Three dimensional structure and functional investigations will examine early (attachment, entry, uncoating) and late (assembly, exit from the host cell, transmission to other cells) stages of viral infection. The principal tools will be X-ray crystallography (Friedman, Smith, Rossmann), EM (Baker, Friedman, Kuhn, Rossmann), molecular biology (Kuhn, Friedman) and NMR (Post, Kuhn, Rossmann, Smith). Viral infectivity will be probed with antibodies, site-directed and selected mutations, antiviral agents that block specific stages in the infectious process, soluble and membrane-bound receptors, pH and temperature variation, and changes of the environment that alter capsid stability. The viruses currently under investigation at Purdue include picornaviruses, alphaviruses, flaviviruses, parvoviruses and retroviruses infecting vertebrates; parvoviruses infection agents; cucumber mosaic virus infection plants; and various bacterial viruses. Only some of these studies are to be funded by this application. The proximity of the groups on the same floor of one building permits exchange of crystallographic expertise (Friedman, Rossmann, Smith) as well as virological and molecular biological techniques (Kuhn, Sanders, Friedman, Smith). Collaborations on specific virus systems are in progress on picornaviruses (Rossmann, Kuhn, Smith, Baker), alphaviruses (Kuhn, Rossmann, Smith, Post) and retroviruses (Sanders, Rossmann and Post).